Emerging viruses present a serious threat to human health and safety. In the past few decades, many infectious diseases, such as those caused by the human immunodeficiency virus (HIV), Ebola virus (EBOV), Nipah (NiV), and Hendra (HeV) viruses, have effectively made the jump from animal to human hosts and devastated entire populations and economies.
In 2012, a novel human coronavirus, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), was isolated from a Saudi Arabian patient suffering from severe pneumonia who later died of respiratory and renal failure (see Zaki et al., N Engl. J. Med., 367: 1814-1820 (2012)). Like other coronaviruses, the MERS-CoV virion utilizes a large surface spike (S) glycoprotein for interaction with and entry into the target cell. The S glycoprotein consists of a globular S1 domain at the N-terminal region, followed by membrane-proximal S2 domain, a transmembrane domain and an intracellular domain. Determinants of cellular tropism and interaction with the target cell are within the S1 domain, while mediators of membrane fusion have been identified within the S2 domain. Through co-purification with the MERS-CoV S1 domain, dipeptidyl peptidase 4 (DPP4, also called CD26) was identified as cellular receptor for MERS-CoV. DDP4 is expressed on the surface of several cell types, including those found in human airways, and possesses ectopeptidase activity, although this enzymatic function does not appear to be essential for viral entry.
To date, MERS-CoV has infected 130 humans from the Middle East to Western Europe with a high mortality rate killing at least 58 humans. MERS-CoV is able to transmit from human to human.
The severity of diseases and high mortality caused by MERS-CoV and the possibility of human-to-human transmission pose a serious threat to public health and urgently require the development of therapeutics and vaccines.
Currently there are no effective therapeutics against MERS-CoV. In September 2013, a report was published describing reduction of MERS-CoV replication and improvement of clinical outcome in rhesus macaques treated with IFN-α2b and ribavirin, which may work primarily by reducing damaging inflammation of the lung and promoting healing by altering the host response, rather than directly targeting the virus (see Falzarano et al., Nature Medicine, 9: 1313-1317 (2013)). However, the treatment was initiated soon (8 hours) after challenge and the disease in the macaques was at best mild to moderate in severity, so whether the drug cocktail would work when faced with severe human disease, which may take longer to develop, remains unclear. In addition, the same two-drug combination has already been used on MERS-CoV patients in Saudi Arabia with less-than-positive results, according to the country's deputy health minister, Doctor Ziad A. Memish, although the drugs were supplied at too late a stage (see Momattin et al., Int. J. Infect. Dis., 17(1): e792-798 (October 2013)). There are no targeted therapies available against the MERS-CoV.
There is a desire for the development of therapeutics and vaccines against MERS-CoV.